Olencki T, Peereboom D, Wood L, Budd G T, Novick A, Finke J, McLain D, Elson P, Bukowski R M
Experimental Therapeutics Program, Cleveland Clinic Taussig Cancer Center, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
J Cancer Res Clin Oncol. 2001 May;127(5):319-24. doi: 10.1007/s004320000211.
A phase I followed by a phase II trial utilizing rIL-2, IFN alpha, and 5-FU were conducted in patients with unresectable and/or metastatic renal cell carcinoma.
Treatment consisted of: rIL-2 at 5.0 x 10(6) IU/m2 SQ on days 1-5 for 4 weeks, rHUIFN alpha-2a at 5.0 x 10(6) U/m2 SQ on days 1, 3, and 5 for 4 weeks, and 5-FU by IV bolus on days 1-5 during week 1. In the phase I study, patients were treated at varying doses of 5-FU: I-none, II-250 mg/m2, III-300, and IV 375. A phase II trial was then conducted utilizing the same schedule and maximum tolerated dose (MTD) for 5-FU.
Twenty patients were entered into the phase I trial. Dose-limiting toxicity included grade III nausea and vomiting, and one sudden cardiac death. The MTD for 5-FU was determined to be 300 mg/m2. In the phase II trial, a median of two cycles of therapy was administered to 25 evaluable patients. Toxicity was moderate and consisted primarily of fevers, chills, fatigue, nausea/vomiting, and anorexia. Grade IV thrombocytopenia, consistent with ITP, developed in one patient each on the phase I and phase II trial. Seven partial responses were seen among 25 patients treated in the phase II trial for a 28% (CI 12-49%) response rate.
The addition of 5-FU to rIL-2 and rHuIFN alpha-2a appears to increase the toxicity of this therapy. Randomized trials will be required to determine if efficacy is enhanced.
对无法切除和/或转移性肾细胞癌患者开展了一项I期试验，随后进行了II期试验，使用了重组白细胞介素-2（rIL-2）、α干扰素（IFNα）和5-氟尿嘧啶（5-FU）。
治疗方案包括：第1至5天皮下注射rIL-2，剂量为5.0×10⁶IU/m²，共4周；第1、3和5天皮下注射重组人α干扰素-2a（rHUIFNα-2a），剂量为5.0×10⁶U/m²，共4周；第1周的第1至5天静脉推注5-FU。在I期研究中，患者接受不同剂量的5-FU治疗：I组 - 无，II组 - 250mg/m²，III组 - 300mg/m²，IV组 - 375mg/m²。随后进行II期试验，采用相同的方案和5-FU的最大耐受剂量（MTD）。
20名患者进入I期试验。剂量限制性毒性包括III级恶心和呕吐，以及1例心源性猝死。5-FU的MTD确定为300mg/m²。在II期试验中，25名可评估患者接受了中位两个周期的治疗。毒性为中度，主要包括发热、寒战、疲劳、恶心/呕吐和厌食。在I期和II期试验中，各有1名患者出现与免疫性血小板减少性紫癜（ITP）一致的IV级血小板减少。在II期试验治疗的25名患者中观察到7例部分缓解，缓解率为28%（置信区间12 - 49%）。
在rIL-2和rHuIFNα-2a中添加5-FU似乎会增加该疗法的毒性。需要进行随机试验以确定疗效是否得到提高。
